National Cerebral and Cardiovascular


Research Institute

Department of Cardio Vascular Aging



Director Ippei Shimizu
Laboratory Chief Naofumi Yoshida
Staff Scientist Yung Ting Hsiao
Research Fellow Tin May Aung
Chun-Han Chang
JSPS Research Fellow Agian Jeffilano Barinda
Intern Student Tom Yoshizaki
Ryota Kubo
Research assistant Yuki Shimomura
Tomomi Yamamoto
Junko Kano


<Missions of our lab>
Our mission is to generate new therapies and establish novel therapeutic concepts for cardiovascular diseases. For this aim, we focus on aging, and try to suppress or even reverse unfavorable aspects of this biological process (Nat Med 2009、J Clin Invest 2010、2014、Cell Metab 2012、2013、J Mol Cell Cardiol 2015、2019、Cell Rep 2018、Sci Rep 2019、2021、2021、2022、Nature Aging 2021、iScience 2021、2022、2022).
We define “Senocules” in circulation as molecules that contribute for the acceleration of aging, and these include “Senometabolite” and “Senoprotein”. We are trying to establish the concept “Senocule-induced synchronized aging (sync-aging)”. Recently, we defined two new concepts for diseases; Age-related fibrotic disorders (A-FiD), and Senometabolite Related Disorders (SRDs). With global members, we are now trying to establish next generation therapies for these disorders (Figure).

Keywords of our research; Heart failure, Aging, A-FiD, SRDs


1. Furuuchi R*, Shimizu I*,**, Yoshida Y, Katsuumi G, Suda M, Kubota Y, Walsh K, Minamino T. Endothelial SIRT-1 has critical role for the maintenance of capillarization in brown adipose tissue. iScience. 2022 Nov18, 25, 105424.

2. Yoshida Y*, Shimizu I*,**, Shimada A, Nakahara K, Yanagisawa S, Kubo M, Fukuda S, Ishii C, Yamamoto H, Ishikawa T, Kano K, Aoki J, Hayashi Y, Ikegami R, Katsuumi G, Suda M, Ozaki K, Kashimura T, Izumi D, Yoshida Y, Okuda S, Ohta S, Okamoto S, Minokoshi Y, Oda K, Sasaoka T, Abe M, Sakimura K, Kubota Y, Yoshimura N, Kajimura S, Zuriaga M, Walsh K, Soga T** and Minamino T**. Brown adipose tissue dysfunction promotes heart failure via a trimethylamine N-oxide-dependent mechanism. Sci Rep. 2022 Sep 1;12(1):14883.

3. Hayashi Y*, Shimizu I*,**, Yoshida Y*, Ikegami R, Suda M, Katsuumi G, Nakao M, Fujiki S, Abe M, Sakimura K, Okuda S, Hayano T, Walsh K, Jespersen NJ, Nielsen S, Scheele C, Minamino T**. Coagulation factors promote brown adipose tissue dysfunction and abnormal systemic metabolism in obesity. iScience. 2022 Jun 7;25(7):104547.

4. Suda M*, Shimizu I*, Katsuumi G, Yoshida Y, Matsumoto N, Yoshida Y, Katayama A, Wada J, Seki M, Suzuki Y, Okuda S, Ozaki K, Matsui M, Minamino T. Glycoprotein nonmetastatic melanoma protein B regulates lysosomal integrity and lifespan of senescent cells. Sci Rep. 2022, April 20, 6522.

5. Yoshida Y*, Shimizu I*, Yung Ting Hsiao*, Hayashi Y, Suda M, Katsuumi G, Ikegami R, Nakao M, Sakai R, Seki M, Suzuki Y, Okuda S, Soga T, Minamino T. Differing impact of phosphoglycerate mutase 1-deficiency on brown and white adipose tissue. iScience. 2022 Apr 18;25(5):104268

6. Park N, Marquez J, Pham T, Ko TH, Youm JB, Kim M, Choi SH, Moon J, Flores J, Ko K, Rhee BD, Shimizu I, Minamino T, Ha JD, Hwang JY, Yang SJ, Park CS, Kim HK and Han J. Cereblon contributes to cardiac dysfunction by degrading Cav1.2α. European Heart Journal. 2022, May21;43(20):1973-1989.

7. Suda M*, Shimizu I*, Katsuumi G, Yoshida Y, Hayashi Y, Ikegami R, Matsumoto N, Yoshida Y, Mikawa R, Katayama A, Wada J, Seki M, Suzuki Y, Iwama A, Nakagami H, Nagasawa A, Morishita R, Sugimoto M, Okuda S, Tsuchida M, Ozaki K, Matsui M, Minamino T. Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice. Nature aging. 2021, Dec; 10.

8. Cho K, Ushiki T, Ishiguro H Tamura S, Araki M, Suwabe T, Katagiri T, Ohashi R, Ajioka Y, Shimizu I, Okuda S, Masuko M, Nakagawa Y, Hirai H, Alexander W, Shimano H, Sone H. Altered Microbiota by a High-Fat Diet Accelerates Lethal Myeloid Hematopoiesis Associated with Systemic Socs3 Deficiency. iScience. 2021, Oct; 24(10), 103117.

9. Nakao M, Shimizu I*,**, Katsuumi G, Yoshida Y, Suda M, Hayashi Y, Ikegami R, Hsiao Yung Ting, Okuda S, Soga T, Minamino T**. Empagliflozin Maintains Capillarization and Improves Cardiac Function in a Murine Model of Left Ventricular Pressure Overload. Sci Rep. 2021, Sep15;11(1): 18384 (2021).

10. Hsiao YT*, Shimizu I*,**, Wakasugi T, Jiao S, Watanabe T, Yoshida Y, Ikegami R, Hayashi Y, Suda M, Katsuumi G, Nakao M, Ozawa T, Kashimura T, Ozaki K, Hanawa H, Minamino T**. Cardiac Mitofusin-1 is Reduced in Non-responding Patients with Idiopathic Dilated Cardiomyopathy. Sci Rep. 2021, Mar24; 11(1):6722.

11. Kim HK, Ko T, Song I, Jeong Y, Heo HJ, Jeong S, Kim M, Park NM, Seo DY, Kha PT, Kim SW, Lee SR, Cho SW, Won JC, Youm JB, Ko K, Rhee B, Kim N, Cho KI, Shimizu I, Minamino T, Ha NC, Park Y, Nilius B, Han J. BH4 activates CaMKK2 and rescues the cardiomyopathic phenotype in rodent models of diabetes. Life Science Alliance.. 2020 Jul 22;3(9):e201900619.

last updated : 2024/04/05

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